title: Association of PAI-1 and fibrinogen with diabetic retinopathy in the Veterans Affairs Diabetes Trial (VADT).
abstract: OBJECTIVE
  To test the hypothesis that high levels of plasminogen-activating inhibitor (PAI)-1 and fibrinogen at baseline were associated with the onset or progression of diabetic retinopathy (DR) during the Veterans Affairs Diabetes Trial (VADT).
  
  
  METHODS
  The VADT was an open-label, prospective, randomized controlled trial to test the effect of standard glycemic control (STD) compared with intensive control (INT) on cardiovascular events in patients with advanced type 2 diabetes mellitus (T2DM). Diabetic retinopathy (DR) outcomes were also collected. Incidence and progression of DR were assessed by grading seven-field stereoscopic fundus photographs at baseline and 5 years later taken in 858 of a total of 1,791 participants who completed both eye examinations.
  
  
  RESULTS
  Assignment to INT was not independently associated with decreased risk of onset of DR. However, after adjustment for multiple covariates, baseline level of PAI-1 was an independent risk factor for the onset of DR. The risk for incidence of DR increased by 12% for each 10 ng/dL increase in baseline PAI-1 concentration (odds ratio [OR] 1.012 [95% CI 1.00-1.024], P = 0.042). Assignment to INT was not independently associated with decreased risk of progression of DR. However, there was an interaction between glycemic treatment assignment and fibrinogen level at baseline. INT was associated with decreased progression of retinopathy in those with fibrinogen <296 mg/dL (OR 0.55 [95% CI 0.31-1.00], P = 0.03).
  
  
  CONCLUSIONS
  The results require confirmation but are consistent with greater hypercoagulabilty and inflammation, as measured by higher levels of PAI-1 and fibrinogen, being related to DR and responsiveness to INT.
authors.affiliation: Corresponding author: Nasrin Azad, nasrin.azad@va.gov.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Azad
authors.forename: Lily
authors.initials: L
authors.lastname: Agrawal
authors.forename: Nicholas V
authors.initials: NV
authors.lastname: Emanuele
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.forename: Gideon D
authors.initials: GD
authors.lastname: Bahn
authors.forename: Madeline
authors.initials: M
authors.lastname: McCarren
authors.forename: Peter
authors.initials: P
authors.lastname: Reaven
authors.forename: Rodney
authors.initials: R
authors.lastname: Hayward
authors.forename: William
authors.initials: W
authors.lastname: Duckworth
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D011446:Prospective Studies; D014728:Veterans
chemical_list: D001786:Blood Glucose; D017395:Plasminogen Activator Inhibitor 1; D005340:Fibrinogen